The detection and analysis of rare blood biomarkers is necessary for early diagnosis of cancer and to facilitate the development of tailored therapies. However, current methods for the isolation of circulating tumour cells (CTCs) or nucleic acids present in a standard clinical sample of only 5–10 ml of blood provide inadequate yields for early cancer detection and comprehensive molecular profiling. Here, we report the development of a flexible magnetic wire that can retrieve rare biomarkers from the subject’s blood in vivo at a much higher yield. The wire is inserted and removed through a standard intravenous catheter and captures biomarkers that have been previously labelled with injected magnetic particles. In a proof-of-concept experiment in a live porcine model, we demonstrate the in vivo labelling and single-pass capture of viable model CTCs in less than 10 s. The wire achieves capture efficiencies that correspond to enrichments of 10–80 times the amount of CTCs in a 5-ml blood draw, and 500–5,000 times the enrichments achieved using the commercially available Gilupi CellCollector.
PurposeTo evaluate whether yogurt supplemented with a probiotic strain could protect middle-aged and elderly people from acute upper respiratory tract infections (URTI) using a randomized, blank-controlled, parallel-group design.Patients and methodsTwo hundred and five volunteers aged ≥45 years were randomly divided into two groups. The subjects in the intervention group were orally administered 300 mL/d of yogurt supplemented with a probiotic strain, Lactobacillus paracasei N1115 (N1115), 3.6×107 CFU/mL for 12 weeks, while those in the control group retained their normal diet without any probiotic supplementation. The primary outcome was the incidence of URTI, and changes in serum protein, immunoglobulins, and the profiles of the T-lymphocyte subsets (total T-cells [CD3+], T-helper cells [CD4+], and T-cytotoxic-suppressor cells [CD8+]) during the intervention were the secondary outcomes.ResultsCompared to the control group, the number of persons diagnosed with an acute URTI and the number of URTI events significantly decreased in the intervention group (P=0.038, P=0.030, respectively). The risk of URTI in the intervention group was evaluated as 55% of that in the control group (relative risk =0.55, 95% CI: 0.307–0.969). The change in the percentage of CD3+ cells in the intervention group was significantly higher than in the control group (P=0.038). However, no significant differences were observed in the total protein, albumin, globulin, and prealbumin levels in both groups (P>0.05).ConclusionThe study suggested that yogurt with selected probiotic strains such as N1115 may reduce the risk of acute upper tract infections in the elderly. The enhancement of the T-cell-mediated natural immune defense might be one of the important underlying mechanisms for probiotics to express their anti-infective effects.
Background Relationships between iron‐dependent ferroptosis and nerve system diseases have been recently revealed. However, the role of ferroptosis in neuropathic pain (NeP) remains to be elucidated. Thus, we aimed to investigate whether ferroptosis in spinal cord contributes to NeP induced by a chronic constriction injury (CCI) of the sciatic nerve. Methods Forty Sprague‐Dawley rats received CCI or sham surgery, and were randomly assigned to the following four groups: sham group; CCI + LIP group; CCI + Veh group; and CCI group. Liproxstatin‐1 or corn oil were separately injected intraperitoneally for three consecutive days after surgery in the CCI + LIP or CCI + Veh group. The mechanical and thermal hypersensitivities were tested after surgery. Biochemical and morphological changes related to ferroptosis in the spinal cord were also assessed. These included iron content, glutathione peroxidase 4 (GPX4) and anti‐acyl‐CoA synthetase long‐chain family member 4 (ACSL4) expression, lipid peroxidation assays, as well as mitochondrial morphology. Results CCI‐induced NeP was followed by iron accumulation, increased lipid peroxidation and dysregulation of ACSL4 and GPX4. Moreover transmission electron microscopy confirmed the presence of aberrant morphological changes on mitochondrial, such as mitochondria shrinkage and membrane rupture. Furthermore, the administration of liproxstatin‐1 on CCI rats attenuated hypersensitivities, lowered the iron level, decreased spinal lipid peroxidation, restored the dysregulations in GPX4 and ACSL4 levels, and protected against CCI induced morphological changes in mitochondria. Conclusions Our findings indicated the involvement of ferroptosis in CCI induced NeP, and point to ferroptosis inhibitors such as liproxstatin‐1 as potential therapies for hypersensitivity induced by peripheral nerve injury. Significance The spinal ferroptosis‐like cell death was involved in the development of neuropathic pain resulted from peripheral nerve injury, and inhibition of ferroptosis by liproxstatin‐1 could alleviate mechanical and thermal hypersensitivities. This knowledge suggested that ferroptosis could represent a potential therapeutic target for neuropathic pain.
A linear piezoelectric actuator based on the stick-slip principle is presented and tested in this paper. With the help of changeable vertical preload force flexure hinge, the designed linear actuator can achieve both large travel stick-slip motion and high-resolution stepping displacement. The developed actuator mainly consists of a bridge-type flexure hinge mechanism, a compound parallelogram flexure hinge mechanism, and two piezoelectric stacks. The mechanical structure and motion principle of the linear actuator were illustrated, and the finite element method (FEM) is adopted. An optimal parametric study of the flexure hinge is performed by a finite element analysis-based response surface methodology. In order to investigate the actuator’s working performance, a prototype was manufactured and a series of experiments were carried out. The results indicate that the maximum motion speed is about 3.27 mm/s and the minimum stepping displacement is 0.29 μm. Finally, a vibration test was carried out to obtain the first natural frequency of the actuator, and an in situ observation was conducted to investigate actuator’s stick-slip working condition. The experimental results confirm the feasibility of the proposed actuator, and the motion speed and displacement are both improved compared with the traditional stick-slip motion actuator.
A bio-inspired absolute pressure sensor network has been developed. Absolute pressure sensors, distributed on multiple silicon islands, are connected as a network by stretchable polyimide wires. This sensor network, made on a 4’’ wafer, has 77 nodes and can be mounted on various curved surfaces to cover an area up to 0.64 m × 0.64 m, which is 100 times larger than its original size. Due to Micro Electro-Mechanical system (MEMS) surface micromachining technology, ultrathin sensing nodes can be realized with thicknesses of less than 100 µm. Additionally, good linearity and high sensitivity (~14 mV/V/bar) have been achieved. Since the MEMS sensor process has also been well integrated with a flexible polymer substrate process, the entire sensor network can be fabricated in a time-efficient and cost-effective manner. Moreover, an accurate pressure contour can be obtained from the sensor network. Therefore, this absolute pressure sensor network holds significant promise for smart vehicle applications, especially for unmanned aerial vehicles.
Giant magnetoresistive (GMR) sensors have been shown to be among the most sensitive biosensors reported. While high-density and scalable sensor arrays are desirable for achieving multiplex detection, scalability remains challenging because of long data acquisition time using conventional readout methods. In this paper, we present a scalable magnetoresistive biosensor array with an on-chip magnetic field generator and a high-speed data acquisition method. The on-chip field generators enable magnetic correlated double sampling (MCDS) and global chopper stabilization to suppress 1/f noise and offset. A measurement with the proposed system takes only 20 ms, approximately 50× faster than conventional frequency domain analysis. A corresponding time domain temperature correction technique is also presented and shown to be able to remove temperature dependence from the measured signal without extra measurements or reference sensors. Measurements demonstrate detection of magnetic nanoparticles (MNPs) at a signal level as low as 6.92 ppm. The small form factor enables the proposed platform to be portable as well as having high sensitivity and rapid readout, desirable features for next generation diagnostic systems, especially in point-of-care (POC) settings.
The magnetic 1/f noise in miniature anisotropic magnetoresistive sensors has been studied quantitatively, and a linear correlation between sensitivity and magnetic 1/f noise parameter has been observed. The noise level can be effectively reduced by having an IrMn exchange bias layer adjacent to the permalloy layer, as sensing stripes of 2 μm width exhibit 16 times smaller magnetic 1/f noise parameter upon introduction of an IrMn layer. This simple method energetically stabilizes the magnetization fluctuation in permalloy, and lowers the 1/f noise without degrading the sensitivity. The geometry dependences of both noise and sensitivity have also been investigated to better guide future magnetoresistive sensor design.
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